Copper(I)-Promoted Aromatic C(sp2)—H Nitration

doi:10.6023/cjoc202603002

Abstract

Nitroaromatic compounds are important chemical raw materials and intermediates, which are widely used in various fields. The development of mild and generally applicable methods for the nitration of arenes has long been a pursuit in organic chemistry. An efficient C(sp²)—H nitration of arenes was developed, using sodium nitrite or tert-butyl nitrite (TBN) as nitrating reagents, 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) as the oxidant in the presence copper(I) catalysts. The nitrated products were obtained in yields up to 96%. This method demonstrates excellent functional group tolerance, accommodating esters, carbonyls, nitro, cyano, and halogen groups. Furthermore, it exhibits broad substrate scope, encompassing electron-rich and electron-deficient arenes, as well as complex pharmaceutical molecules.

Key words: C(sp²)—H nitration of arene, copper catalysis, 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetra- fluoroborate) (Selectfluor), tert-butyl nitrite, NaNO₂

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Hairui Jin, Jie Qin, Yating Zhao, Wujiong Xia. Copper(I)-Promoted Aromatic C(sp²)—H Nitration[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2733-2742.

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铜(I)促进芳香类C(sp²)—H键的硝化反应

Copper(I)-Promoted Aromatic C(sp²)—H Nitration

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Entry	Oxidant	Nitro source	Additive	T/℃	Yield^b/%
1	Selectfluor	TBN	—	50	12
2	NFSI	TBN	—	50	0
3	K₂S₂O₈	TBN	—	50	0
4	NH₄Ce(NO₃)₆	TBN	—	50	0
5	O₂	TBN	—	50	0
6	Selectfluor	TBN	CuI	50	49
7	Selectfluor	TBN	Cu(OAc)₂•H₂O	50	53
8	Selectfluor	TBN	Cu(MeCN)₄BF₄	50	82 (82)^c
9	Selectfluor	TBN	Fe(acac)₃	50	9
10	Selectfluor	TBN	NiI₂	50	58
11	Selectfluor	TBN	AlCl₃	50	6
12	Selectfluor	NaNO₂	Cu(MeCN)₄BF₄	50	63
13	Selectfluor	Cu(NO₃)₂•3H₂O	Cu(MeCN)₄BF₄	50	0
14	Selectfluor	t-BuNNO₂	Cu(MeCN)₄BF₄	50	0
15	Selectfluor	TBN	Cu(MeCN)₄BF₄	30	38
16	Selectfluor	TBN	Cu(MeCN)₄BF₄	60	66
17	—	TBN	Cu(MeCN)₄BF₄	50	0

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铜(I)促进芳香类C(sp2)—H键的硝化反应